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Metabolism. 1997 Feb;46(2):130-4.

Hypothalamic-pituitary-adrenal axis hypersensitivity to naloxone in opioid dependence: a case of naloxone-induced withdrawal.

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  • 1The Biology of Addictive Diseases Laboratory, The Rockefeller University, New York, NY 10021, USA.


A case of opioid withdrawal precipitated in an opioid-dependent person by low plasma levels of naloxone is presented. In this patient, changes were observed in the hypothalamic-pituitary-adrenal (HPA) axis that preceded the clinical symptoms and adrenergic signs of withdrawal. Plasma naloxone levels were strongly correlated with plasma cortisol levels (P < .0001, R2 = .73, r = .85). In addition, these neuroendocrine changes persisted after adrenergic changes and clinical symptoms had been ameliorated by administration of a short-acting opioid agonist. It is suggested that the HPA axis is a more sensitive indicator of opioid withdrawal than the adrenergic system.

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